Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

Mitochondrial Membrane Protein-Associated Neurodegeneration

Allison Gregory  1 , Thomas Klopstock  2 , Tomasz Kmiec  3 , Penelope Hogarth  4 , Susan J Hayflick  5
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].
Affiliations
Free Books & Documents
Review

Mitochondrial Membrane Protein-Associated Neurodegeneration

Allison Gregory et al.
Free Books & Documents

Excerpt

Clinical characteristics: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is characterized initially by gait changes followed by progressive spastic paresis, progressive dystonia (which may be limited to the hands and feet or more generalized), neuropsychiatric abnormalities (emotional lability, depression, anxiety, impulsivity, compulsions, hallucinations, perseveration, inattention, and hyperactivity), and cognitive decline. Additional early findings can include dysphagia, dysarthria, optic atrophy, axonal neuropathy, parkinsonism, and bowel/bladder incontinence. Survival is usually well into adulthood. End-stage disease is characterized by severe dementia, spasticity, dystonia, and parkinsonism.

Diagnosis/testing: The diagnosis of MPAN is typically established in a proband with suggestive findings and biallelic pathogenic variants (or less commonly a heterozygous pathogenic variant) in C19orf12 identified by molecular genetic testing.

Management: Treatment of manifestations: Pharmacologic treatment of spasticity, dystonia, and parkinsonism; psychiatric treatment of significant neuropsychiatric manifestations; physical, occupational, speech, and other therapies as indicated; nutritional supplements and gastric tube feeding as needed; management of excessive secretions and aspiration risk with glycopyrrolate, transdermal scopolamine patch, and/or tracheostomy as indicated.

Surveillance: Routine follow up by a neurologist for medication management and interval assessment of ambulation, speech, and swallowing (often done every 3-6 months, but may be annual for individuals who are more stable); routine monitoring by occupational therapy / physical therapy, mental health providers, ophthalmology, speech and language therapy, and feeding team is recommended; routine assessment of educational needs and social support.

Genetic counseling: MPAN is inherited in an autosomal recessive or (less commonly) autosomal dominant manner.

  1. Autosomal recessive MPAN. If both parents are known to be heterozygous for an C19orf12 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

  2. Autosomal dominant MPAN. Each child of an affected individual has a 50% chance of inheriting the C19orf12 pathogenic variant.

Once the C19orf12 pathogenic variant(s) in the family have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.

PubMed Disclaimer

Similar articles

  • PLA2G6-Associated Neurodegeneration.
    Gregory A, Kurian MA, Maher ER, Hogarth P, Hayflick SJ. Gregory A, et al. 2008 Jun 19 [updated 2017 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2008 Jun 19 [updated 2017 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301718 Free Books & Documents. Review.
  • Sickle Cell Disease.
    Bender MA, Carlberg K. Bender MA, et al. 2003 Sep 15 [updated 2025 Feb 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2003 Sep 15 [updated 2025 Feb 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301551 Free Books & Documents. Review.
  • Beta-Thalassemia.
    Langer AL. Langer AL. 2000 Sep 28 [updated 2024 Feb 8]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2000 Sep 28 [updated 2024 Feb 8]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301599 Free Books & Documents. Review.
  • Ataxia-Telangiectasia.
    Veenhuis S, van Os N, Weemaes C, Kamsteeg EJ, Willemsen M. Veenhuis S, et al. 1999 Mar 19 [updated 2023 Oct 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 1999 Mar 19 [updated 2023 Oct 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301790 Free Books & Documents. Review.
  • SLC6A3-Related Dopamine Transporter Deficiency Syndrome.
    Spaull RVV, Kurian MA. Spaull RVV, et al. 2017 Jul 27 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2017 Jul 27 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 28749637 Free Books & Documents. Review.
See all similar articles

References

    1. Al Macki N, Rashdi I. A novel deletion mutation of exon 2 of the C19orf12 gene in an Omani family with mitochondrial membrane protein-associated neurodegeneration (MPAN). Oman Med J. 2017;32:66–8. - PMC - PubMed
    1. Bayram E, Peker E, Metzger S, Akbostanct M. Myoclonus, hydrocephalus in mitochondrial protein-associated neurodegeneration. Can J Neurol Sci. 2019;46:628–30. - PubMed
    1. Deschauer M, Gaul C, Behrmann C, Prokisch H, Zierz S, Haack TB. C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis. J Neurol. 2012;259:2434–9. - PubMed
    1. Dogu O, Krebs CE, Kaleagasi H, Demirtas Z, Oksuz N, Walker RH, Paisán-Ruiz C. Rapid disease progression in adult-onset mitochondrial membrane protein-associated neurodegeneration. Clin Genet. 2013;84:350–5. - PubMed
    1. Gagliardi M, Annesi G, Lesca G, Broussolle E, Iannello G, Vaiti V, Gambardella A, Quattrone A. C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation. Parkinsonism Relat Disord. 2015;21:813–6. - PubMed

LinkOut - more resources